MicroRNAs (hereinafter referred to as miRNAs) are short non-coding RNAs identified in the genomes of a wide variety of species. miRNAs were first discovered in 1993 in Caenorhabditis elegans, and this was followed by discovery of miRNAs in many other multicellular organisms. A miRNA is a negative regulator of gene expression, and considered to function mainly by incomplete interaction of base pairs with a sequence in the 3′-untranslated region of a protein-encoding mRNA. Various miRNAs so far known, including those of humans, are registered in miRBase (see http://www.mirbase.org/). The roles of some of these miRNAs are not known. However, it has been revealed that certain miRNAs are involved in regulation of various cellular processes, such as differentiation of adipocytes, maturation of oocytes, maintenance of the pluripotent cellular state and regulation of insulin secretion.
For example, Patent Literature 1 describes a method for regulating expression of a target gene in cells, which method comprises the step of introducing a polynucleotide that forms a double strand with mRNA transcribed from the target gene into the cells. In this method, the region where the double strand is formed comprises a mammalian miRNA target region. It is described that examples of the polynucleotide used in this method include various miRNAs and precursors thereof (pre-miRNAs).
Further, Patent Literature 2 describes various methods and compositions in which miRNAs are involved. More particularly, for example, a method wherein expression analysis of miRNAs is carried out to produce a miRNA profile, and the produced miRNA profile is then used as described. In this method, many miRNAs which may be used to produce usable profiles are described. For example, among these many miRNAs, (hsa-)miR-22 is included. (hsa-)miR-22 is a known miRNA also registered in the above-mentioned miRBase. Patent Literature 2 also describes that these many miRNA profiles can be used for diagnosis of specific diseases, diseased states and disorders. Examples of the specific diseases include cancer.
Further, Patent Literature 3 describes a method and a composition based on a more detailed mechanism, wherein a miRNA or a miRNA inhibitor molecule is involved. More particularly, the literature describes a method for reducing or inhibiting the cell growth, a method for inducing or increasing the cell growth, a method for decreasing the cell survival rate, a method for increasing the cell survival rate, a method for increasing apoptosis of cells, and a method for inhibiting apoptosis of cells, which methods comprise the step of introducing an effective amount of a specific synthetic miRNA molecule to cells.
Patent Literature 3 also partially describes functions of the above-mentioned (hsa-)miR-22 among such miRNAs. More particularly, it is described that (hsa-)miR-22 is a miRNA which significantly decreases the number of living A549 cells (human lung cancer cells) and significantly increases the percentage of apoptotic cells. Further, a method for treating cancer in a subject, which method uses such a function and comprises the step of administration of an effective amount of a synthetic miRNA molecule corresponding to (hsa-)miR-22 to the subject, is also described.
On the other hand, precursor cells of most animal cells stop their growth after specific numbers of times of division, and remain in the terminally-differentiated state. The mechanism to stop the division has not been completely elucidated. However, such a cell growth inhibition mechanism in the cell has been elucidated to some extent for human fibroblasts. More particularly, it has been revealed that the growth rate decreases in the late mitotic period, and the cells then stop dividing and enter a non-dividing state, in which the cells never grow again. This phenomenon is called cellular senescence due to replication (see Non-patent Literature 1).